Management of Celiac Disease: Beyond the Gluten-Free Diet

Crowe, Sheila E.

doi:10.1053/j.gastro.2014.04.027

Cited by 7 publications

(5 citation statements)

References 20 publications

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“…A number of non-dietary therapies are currently under investigation that target specific aspects of CeD pathogenesis including intraluminal agents, immunomodulators and vaccination ( 267 , 268 ) . Larazotide acetate (AT-1001), a peptide derived from cholera toxin, is thought to regulate intestinal paracellular permeability by inhibiting the disassembly of intestinal TJ.…”

Section: Peptide Permeabilitymentioning

confidence: 99%

Intestinal barrier dysfunction: implications for chronic inflammatory conditions of the bowel

Miner-Williams

Moughan

2016

Nutr. Res. Rev.

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The intestinal epithelium of adult humans acts as a differentially permeable barrier that separates the potentially harmful contents of the lumen from the underlying tissues. Any dysfunction of this boundary layer that disturbs the homeostatic equilibrium between the internal and external environments may initiate and sustain a biochemical cascade that results in inflammation of the intestine. Key to such dysfunction are genetic, microbial and other environmental factors that, singularly or in combination, result in chronic inflammation that is symptomatic of inflammatory bowel disease (IBD). The aim of the present review is to assess the scientific evidence to support the hypothesis that defective transepithelial transport mechanisms and the heightened absorption of intact antigenic proinflammatory oligopeptides are important contributing factors in the pathogenesis of IBD.

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Section: Peptide Permeabilitymentioning

confidence: 99%

Intestinal barrier dysfunction: implications for chronic inflammatory conditions of the bowel

Miner-Williams

Moughan

2016

Nutr. Res. Rev.

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“…17, 18 This multicenter, randomized, placebo-controlled trial is the largest reported clinical trial conducted in CeD and was designed to assess efficacy and safety of larazotide acetate as an adjunct to a GFD in adult patients with persistent symptoms despite maintenance of a long term GFD. A secondary objective was to validate the Celiac Disease Patient Reported Outcome (CeD PRO) instrument as a daily measure of therapeutic effects.…”

Section: Introductionmentioning

confidence: 99%

Larazotide Acetate for Persistent Symptoms of Celiac Disease Despite a Gluten-Free Diet: A Randomized Controlled Trial

et al. 2015

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Background & Aims Celiac disease (CeD) is a prevalent autoimmune condition. Recurrent signs and symptoms are common despite treatment with a gluten free diet (GFD), yet no approved or proven non-dietary treatment is available. Methods In this multicenter randomized, double-blind, placebo-controlled study, we assessed larazotide acetate 0.5, 1, or 2 mg three times daily to relieve ongoing symptoms in 342 adults with CeD who had been on a GFD for ≥12 months and maintained their current GFD during the study. The study included a 4-week placebo run-in, 12-week treatment, and 4-week placebo run-out phase. The primary endpoint was the difference in average on-treatment Celiac Disease Gastrointestinal Symptom Rating Scale score (CeD-GSRS). Results The primary endpoint was met at the 0.5 mg dose of larazotide acetate with fewer symptoms compared with placebo by Modified Intention to Treat (n=340) (ANCOVA p=0.022, MMRM p=0.005). The 0.5mg dose showed effect on exploratory endpoints including, 26% decrease in Celiac Disease Patient Reported Outcome Symptomatic Days (p=0.017); 31% increase in Improved Symptom Days (p=0.034); ≥50% reduction from baseline of weekly average Abdominal Pain Score for ≥6 out of 12 weeks of treatment (p=0.022); and a decrease in Non-GI symptoms of headache and tiredness (p=0.010). The 1 and 2 mg doses were no different than placebo for any endpoint. Safety was comparable to placebo. Conclusions Larazotide acetate 0.5 mg reduced signs and symptoms in CeD patients on a GFD better than a GFD alone. While results were mixed, this study represents the first successful trial of a novel therapeutic agent targeting Tight Junction regulation in patients with CeD who are symptomatic despite a GFD. Clinicaltrials.gov, NCT01396213

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“…The elimination of gluten from diets is occurring worldwide. [54] Reduced inflammation is one significant benefit from adhering to a GFD. [19] Nutritional deficiencies can be identified and remedied given sufficient support.…”

Section: Perceived Benefits Of Gfdmentioning

confidence: 99%

“…[19] Nutritional deficiencies can be identified and remedied given sufficient support. [54] Ma et al [10] provide a recommended flow chart for pursuing a diagnosis that is more inclusive of the diverse array of phenotypes that reflect pathological responses to gluten. They also downplay the importance of the biopsy.…”

Section: Perceived Benefits Of Gfdmentioning

confidence: 99%

Community Based Pilot Study of Diagnostic Paths to the Gluten Free Diet

Stevenson

Rankin-Sunter²,

Maki³

et al. 2016

IJCD

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Wheat consumption is increasing worldwide and also increasing is the frequency of celiac disease (CeD), a pathological response to wheat protein (gluten) in genetically susceptible individuals. Non-celiac gluten sensitivity (NCGS) is another, less studied wheat-induced pathology. The treatment for both is a gluten-free diet (GFD). More individuals choose the diet than predicted by the epidemiological 1-2% prevalence. A preliminary survey by questionnaire asked members and attendees of the local gluten information group (GIG) meetings and functions about their diagnostic experiences and symptom levels in order understand the increased demand for gluten-free foods. Same-aged and-sex friends participated as a comparative "control". Mixed methods were used including content analyses of prose narratives and independent and paired t tests of symptom levels measured with Likert scales. This convenience sample, surveyed in 2011-2012, is mostly female (54 F, 5 M) with an average age of 54.6 ± 2.0 years. Most participants consulted medical professionals with mean time to diagnosis of 7 years determined mostly from "classic" presenting symptoms. Negative biopsies or blood tests and atypical symptoms that overlap other conditions delayed diagnosis. There were 43 and 16 participants with CeD and NCGS, respectively differing little in symptom levels. Self-diagnosis and use of naturopaths account for some of the "excess" individuals. General practitioners should be encouraged to get additional nutrition training and to discuss with patients dietary choices that support wellness and minimize the risk for pathological immune responses. Patients with CeD particularly need support and follow-up in the transition to a GFD.

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Management of Celiac Disease: Beyond the Gluten-Free Diet

Cited by 7 publications

References 20 publications

Intestinal barrier dysfunction: implications for chronic inflammatory conditions of the bowel

Intestinal barrier dysfunction: implications for chronic inflammatory conditions of the bowel

Larazotide Acetate for Persistent Symptoms of Celiac Disease Despite a Gluten-Free Diet: A Randomized Controlled Trial

Community Based Pilot Study of Diagnostic Paths to the Gluten Free Diet

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